PB0676 - Spleen Microbiota Dysbiosis Play a Role in Response to Splenectomy in Patients with Primary Immune Thrombocytopenia: a Prospective Cohort Study

Monday, June 24, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Jia Chen, MD

tianjin
Chinese academy of medical sciences
Tianjin, Tianjin, China (People's Republic)

Co-Author(s)

TS

Ting Sun

Tianjin
Chinese academy of medical science
Tianjin, Tianjin, China (People's Republic)
YC

Yunfei Chen

Tianjin
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases
Tianjin, Tianjin, China (People's Republic)
Yang Li, Master student

Tianjin
Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Tianjin, China (People's Republic)
Renchi Yang, MD

Head of Thrombosis and Hemostasis Center
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tianjin, Hebei, China (People's Republic)
LZ

Lei Zhang

professor
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China
Tianjin, Tianjin, China (People's Republic)

Background: The gut microbiota exhibited an altered composition in primary immune thrombocytopenia (ITP), and corticosteroid-resistant ITP patients exhibited a gut microbiome composition distinct from that of treatment-naïve ones. It is well known that a robust immunological response occurs within the spleens of ITP. However, the role of spleen microbiome alterations on the pathogenesis of ITP remained to be defined.

Aims: To investigate the spleen microbiome in ITP patients who received splenectomy, and identify splenic microbial components associated with the response to splenectomy.

Methods: Patients followed in this study were enrolled in National Longitudinal Cohort of hematological Diseases (NICHE, NCT04645199). The spleen microbiome was screened by 5R 16S rRNA gene sequencing. Random forest (RF) algorithm to select the candidate biomarker. PICRUSt2 software was used to infer the functional gene composition of microbiome.

Results: This prospective cohort study enrolled twenty-four ITP patients who underwent splenectomy, including responders (n=16) and non-responders (n=8). Examination of the rarefaction curves indicated that the responder group displayed a greater species richness in their spleen microbiota compared to the non-responder group. On genus level, there were five microbiomes that were primarily enriched in the responder group, and 19 were enriched in the nonn-responder group by LefSe analysis. Williamsia marianensis, and Williamsia were selected by RF algorithm, as final predictors for the response of splenectomy, and the AUC values were 0.836 (95%CI: 0.623-1.000), 0.820 (95%CI: 0.588-1.000), respectively. Comparing the groups, a total of ten gene metabolic pathways at level 2 showed significant differences. Among then, carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways were primarily enriched in the non-responder group.

Conclusion(s): Our study firstly established a gene catalog for ITP spleen microbiota, and identified their compositional and functional alterations, which help to elucidate the pathogenesis of resistance to splenectomy.